Genetic Variant ZNF789:c.25-1453T>C (chr7-99478208-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_213603.3(ZNF789):c.25-1453T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 1,155,498 control chromosomes in the GnomAD database, including 5,944 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1570 hom., cov: 32)

Exomes 𝑓: 0.088 ( 4374 hom. )

Consequence

ZNF789
NM_213603.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.469

Publications

26 publications found

Variant links:

Genes affected

ZNF789 (HGNC:27801): (zinc finger protein 789) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF789 links:

ZNF394 (HGNC:18832): (zinc finger protein 394) The protein encoded by this gene is a zinc finger protein that inhibits the transcription of mitogen-activated protein kinase signaling pathways. The encoded protein may be involved in cardiac function. [provided by RefSeq, Sep 2016]

ZNF394 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF789	NM_213603.3 link	c.25-1453T>C		intron_variant	Intron 2 of 4	ENST00000331410.10	NP_998768.2	Q5FWF6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF789	ENST00000331410.10 link	c.25-1453T>C		intron_variant	Intron 2 of 4	1	NM_213603.3	ENSP00000331927.5		Q5FWF6-1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19071

AN:

151994

Hom.:

1561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.0987

Gnomad ASJ

AF:

0.0755

Gnomad EAS

AF:

0.00385

Gnomad SAS

AF:

0.0661

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0831

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.0878

AC:

88073

AN:

1003386

Hom.:

4374

AF XY:

0.0872

AC XY:

42942

AN XY:

492472

show subpopulations

African (AFR)

AF:

0.236

AC:

5108

AN:

21620

American (AMR)

AF:

0.0859

AC:

2223

AN:

25878

Ashkenazi Jewish (ASJ)

AF:

0.0796

AC:

1101

AN:

13836

East Asian (EAS)

AF:

0.00194

AC:

AN:

11834

South Asian (SAS)

AF:

0.0681

AC:

4862

AN:

71414

European-Finnish (FIN)

AF:

0.149

AC:

1825

AN:

12284

Middle Eastern (MID)

AF:

0.0888

AC:

254

AN:

2860

European-Non Finnish (NFE)

AF:

0.0861

AC:

69529

AN:

807232

Other (OTH)

AF:

0.0864

AC:

3148

AN:

36428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

3729

7458

11186

14915

18644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3074

6148

9222

12296

15370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.126

AC:

19109

AN:

152112

Hom.:

1570

Cov.:

AF XY:

0.128

AC XY:

9493

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.225

AC:

9322

AN:

41466

American (AMR)

AF:

0.0985

AC:

1506

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0755

AC:

262

AN:

3472

East Asian (EAS)

AF:

0.00386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0666

AC:

321

AN:

4822

European-Finnish (FIN)

AF:

0.160

AC:

1689

AN:

10584

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0831

AC:

5653

AN:

67990

Other (OTH)

AF:

0.125

AC:

264

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

813

1627

2440

3254

4067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0932

Hom.:

825

Bravo

AF:

0.125

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.7

(source)

DANN

Benign

0.50

PhyloP100

-0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over